12-0-Tetradecanoyl-phorbol-13-acetate (TPA), the most powerful tumor promotor in the phorbol series, initiates a series of metabolic events in granulocytes which are also activated during phagocytosis. Cells of the HL-60 line, derived from peripheral blood leukocytes of a patient with promyelocytic leukemia, can be induced to mature towards a granulocytic phenotype by growth in the presence of DMSO. During this in vitro maturation the cells achieve the ability to respond to TPA as measured by an increase in hexose monophosphate shunt activity and protease production. The cell line possesses Fc and C3b receptors. When cells are induced to mature the levels of C3b receptor activity increase. On this basis, I propose to study the development of TPA-responsive systems during the maturation of human myeloid cells in vitro to determine: 1. Whether the enzymatic activities involved in the response of granulocytes to TPA can be detected prior to development of TPA sensitivity. 2. Whether other tumor promotors induce the same responses. 3. Whether all of the enzymatic activities involved in the TPA response appear simultaneously or sequentially. 4. Whether TPA has an effect on the surface receptor activity of these myeloid cells and how the effect correlates with the expression of biochemical characteristics. 5. Whether anti-inflammatory glucocorticoids, which interfere with tumor promotion, have any selective effect on the occurrence or activity of the enzyme involved in the TPA response. 6. Whether the possibility exists to extend these studies to other diseases involving impaired neutrophil function.